Distinct populations suppress or escalate intake of cocaine paired with aversive quinine.

BACKGROUND: Only a subset of individuals who encounter illicit drugs become persons with a substance use disorder. Individual differences in aversive reactions to drug-associated phenomena like smoke inhalation and unpleasant taste are predictors for continued use. While several preclinical studies have explored self-administration involving aversive cues, none have simultaneously introduced aversion with the initial drug self-administration. We aimed to develop such a model by pairing intravenous cocaine with intraoral quinine self-administration from the outset and investigate whether repeated exposure to an aversive stimulus would alter its hedonic value under laboratory conditions.

METHODS: Twenty-seven male and female Sprague Dawley rats self-administered intravenous/intraoral (cocaine/quinine) for 2h/day over 14 days. This was followed by a 1-day quinine-only extinction session, a 3-day return to self-administration, and an intraoral infusion session to assess quinine taste reactivity (TR).

RESULTS: We identified three distinct groups. The first self-administered very little cocaine, while the second sharply escalated cocaine intake. Both groups had similar aversive TR to quinine, suggesting that the escalating group did not habituate to the aversive cue but pursued drug despite it. We also identified a third group with high initial intake that decreased over time. This decrease predicted high aversive TR, and we argue this group may represent individuals who engage in excessive use on their first encounter and subsequently find self-administration to be aversive.

CONCLUSIONS: Our novel model yields three distinct groups that differ in self-administration patterns and aversive cue valuation.